Exploratory, Randomized, Dose-Response Study of the Anti-PD-L1 Antibody HFC-L1/c4G12 in Dogs with Pulmonary Metastatic Oral Malignant Melanoma
Oral malignant melanoma (OMM) is a highly aggressive malignancy in dogs. The development of effective systemic therapies is urgently required to improve the treatment of canine OMM. Immunotherapy using immune checkpoint inhibitors (ICIs) has been investigated in canines following their dramatic success in human cancer treatment; however, there is still a need for extensive veterinary clinical studies to clarify and optimize their clinical benefits. Among the ICIs under development for canine cancer immunotherapy, c4G12 (HFC-L1), a canine chimeric anti-PD-L1 antibody, has shown promising efficacy in dogs with pulmonary metastatic OMM in previous clinical studies. However, the optimal dose of HFC-L1/c4G12 has not yet been determined. To explore the dose-response relationship of HFC-L1, a multicenter, randomized clinical study was conducted using three different doses (2, 5, or 10 mg/kg via intravenous infusion every 2 weeks) to treat dogs with pulmonary metastatic OMM (<i>n</i> = 8-9 per group). The safety profiles were similar among the dose groups, and numerically longer median overall survival was achieved in the higher dose groups (5 and 10 mg/kg) than in the 2 mg/kg group. Although the study was exploratory in nature with a small sample size, 5-10 mg/kg should be considered the preferred dose in future clinical studies using HFC-L1.
Authors
- Keiichi Yamamoto (ORCID: https://orcid.org/0000-0003-3278-5001)
- Takuya Furuta (ORCID: https://orcid.org/0000-0003-2124-5472)
- M. Shiro (ORCID: https://orcid.org/0000-0002-2569-899X)
- Hayato Nakamura (ORCID: https://orcid.org/0000-0003-2115-9873)
- Satoru Konnai (ORCID: https://orcid.org/0000-0002-3230-7109)
- Hiroto Takeuchi
- Tomohiro Okagawa (ORCID: https://orcid.org/0000-0002-1391-9732)
- Naoya Maekawa
- Satoshi Takagi (ORCID: https://orcid.org/0000-0001-6653-5890)
- Ryo Owaki (ORCID: https://orcid.org/0000-0002-9177-9325)
- Akinori Yamauchi (ORCID: https://orcid.org/0000-0001-6900-8949)
- Tomoyuki Abe (ORCID: https://orcid.org/0000-0001-6859-7614)
- Yukinari Kato (ORCID: https://orcid.org/0000-0001-5385-8201)
- Kenji Hosoya (ORCID: https://orcid.org/0000-0001-9208-3736)
- Ayano Kudo
- Kazuhiko Ohashi (ORCID: https://orcid.org/0000-0002-7513-640X)
- Michihito Tagawa (ORCID: https://orcid.org/0000-0003-1645-4413)
- Yasuhiko Suzuki (ORCID: https://orcid.org/0000-0002-1313-1494)
- Yurika Tachibana
- Sangho Kim (ORCID: https://orcid.org/0000-0001-8451-4479)
- Tatsuya Deguchi (ORCID: https://orcid.org/0000-0002-9859-2299)
- Yumiko Kagawa (ORCID: https://orcid.org/0009-0006-0078-1443)
- S Kanazawa
- Shintaro Kamo (ORCID: https://orcid.org/0009-0004-5814-0791)
- Ryohei Kinoshita
- Madoka Yokokawa
Institutions
- Tohoku University (JP)
- Sapporo University (JP)
- Hokkaido University (JP)
- Sapporo Science Center (JP)
- Veterinary Medical Center (JP)
- Hokkaido University Hospital (JP)
- Fuso Pharmaceutical Industries (Japan) (JP)
- Azabu University (JP)
- Obihiro University of Agriculture and Veterinary Medicine (JP)
- Rakuno Gakuen University (JP)
Publication Details
- Journal
- Veterinary Sciences
- Published
- 2025-09-02
- DOI
- https://doi.org/10.3390/vetsci12090850
- Citations
- 1
- Primary Topic
- Veterinary Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 1.52
Funders
- Japan Agency for Medical Research and Development
- Obihiro University of Agriculture and Veterinary Medicine
- Hokkaido University
- Japan Society for the Promotion of Science